BAG5 functionally interacts with the autophagy adaptor protein p62

Molecular chaperones are critical to maintaining intracellular proteostasis and have been shown to have a protective role against alpha-synuclein mediated toxicity. Co-chaperone proteins regulate the activity of molecular chaperones and connect the chaperone network to protein degradation and cell death pathways. Bcl-2 associated athanogene 5 (BAG5) is a co-chaperone that modulates proteostasis by inhibiting the activity of Hsp70 and several E3 ubiquitin ligases, resulting in enhanced neurodegeneration in models of Parkinson’s disease (PD). Here we identify a novel interaction between BAG5 and p62/sequestosome-1 (SQSTM1), suggesting that BAG5 may bridge the chaperone network to autophagy-mediated protein degradation. The interaction was discovered using affinity purifaction followed by mass spectrometry to identify BAG5 interacting proteins and was validated by subsequent in vitro immunoprecipitation studies.